Despite its natural abundance and widespread use as food, paint additive, and in bone implants, no specific biological function of titanium is known in the human body. High concentrations of Ti(IV) could result in cellular toxicity, however, the absence of Ti toxicity in the blood of patients with titanium bone implants indicates the presence of one or more biological mechanisms to mitigate toxicity. Similar to Fe(III), Ti(IV) in blood binds to the iron transport protein serum transferrin (sTf), which gives credence to the possibility of its cellular uptake mechanism by transferrin-directed endocytosis. However, once inside the cell, how sTf bound Ti(IV) is released into the cytoplasm, utilized, or stored remain largely unknown. To explain the molecular mechanisms involved in Ti use in cells we have drawn parallels with those for Fe(III). Based on its chemical similarities with Fe(III), we compare the biological coordination chemistry of Fe(III) and Ti(IV) and hypothesize that Ti(IV) can bind to similar intracellular biomolecules. The comparable ligand affinity profiles suggest that at high Ti(IV) concentrations, Ti(IV) could compete with Fe(III) to bind to biomolecules and would inhibit Fe bioavailability. At the typical Ti concentrations in the body, Ti might exist as a labile pool of Ti(IV) in cells, similar to Fe. Ti could exhibit different types of properties that would determine its cellular functions. We predict some of these functions to mimic those of Fe in the cell and others to be specific to Ti. Bone and cellular speciation and localization studies hint toward various intracellular targets of Ti like phosphoproteins, DNA, ribonucleotide reductase, and ferritin. However, to decipher the exact mechanisms of how Ti might mediate these roles, development of innovative and more sensitive methods are required to track this difficult to trace metal in vivo.

中文翻译：

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探索钛 (IV) 与铁 (III) 的化学接近性，以阐明钛 (IV) 在人体内的功能。


尽管钛天然储量丰富，并广泛用作食品、油漆添加剂和骨植入物，但钛在人体中的具体生物学功能尚不清楚。高浓度的 Ti(IV) 可能会导致细胞毒性，然而，钛骨植入物患者的血液中不存在 Ti 毒性，表明存在一种或多种减轻毒性的生物机制。与 Fe(III) 类似，血液中的 Ti(IV) 与铁转运蛋白血清转铁蛋白 (sTf) 结合，这证实了其通过转铁蛋白引导的内吞作用进行细胞摄取机制的可能性。然而，一旦进入细胞，sTf 结合的 Ti(IV) 如何释放到细胞质中、利用或储存仍然很大程度上未知。为了解释细胞中 Ti 使用的分子机制，我们将其与 Fe(III) 的分子机制进行了比较。基于其与 Fe(III) 的化学相似性，我们比较了 Fe(III) 和 Ti(IV) 的生物配位化学，并假设 Ti(IV) 可以与相似的细胞内生物分子结合。类似的配体亲和力曲线表明，在高 Ti(IV) 浓度下，Ti(IV) 可以与 Fe(III) 竞争结合生物分子，并会抑制 Fe 的生物利用度。在体内典型的 Ti 浓度下，Ti 可能以 Ti(IV) 的不稳定池形式存在于细胞中，类似于 Fe。钛可以表现出不同类型的特性，这些特性将决定其细胞功能。我们预测其中一些功能会模仿细胞中铁的功能，而其他功能则与钛有关。骨和细胞的形态形成和定位研究暗示了 Ti 的各种细胞内靶标，如磷蛋白、DNA、核糖核苷酸还原酶和铁蛋白。 然而，为了破译钛如何介导这些作用的确切机制，需要开发创新且更灵敏的方法来追踪这种难以在体内追踪的金属。